Synthesis method of 1-[4-(chloromethyl) phenyl] ethanone

Abstract

The invention discloses a synthesis method of 1-[4-(chloromethyl) phenyl] ethanone, and belongs to the technical field of organic synthesis. The method comprises the following steps: adding Lewis acid and an acylation reagent into a solvent, dropwise adding benzyl chloride at 0-40 DEG C, carrying out water quenching after the reaction is completed, taking an organic layer, adding an alkali solution to adjust the pH value to 4-7, taking the organic layer, carrying out vacuum concentration until the organic layer is dry, and carrying out vacuum rectification to obtain 1-[4-(chloromethyl) phenyl] ethanone; the molar ratio of the lewis acid to the acylation reagent to benzyl chloride is (1-3): (1.0-1.5): 1, the lewis acid is selected from aluminum trifluoromethanesulfonate or copper trifluoromethanesulfonate, and the acylation reagent is selected from acetyl chloride or acetic anhydride. According to the method, benzyl chloride is used as an initial raw material, and high-purity (the purity reaches 98%) 1-[4-(chloromethyl) phenyl] ethanone is obtained through Friedel-Crafts acylation reaction, quenching and rectification. The method has the advantages of simple process, high yield, suitability for industrial production and the like.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone. Background Art

[0002] 4-Chloromethylstyrene can be used as a component of ion exchange resins, photoresist polymers, cross-linked fibers, coupling agents and conductive polymers, and is the starting material for preparing a variety of copolymers. Its 1,2,3 difunctional monomers are easily substituted by chlorine to form derivatives. 1-[4-(Chloromethyl)phenyl]ethanone is a key intermediate for the industrial synthesis of 4-chloromethylstyrene. At the same time, 1-[4-(Chloromethyl)phenyl]ethanone, as an organic synthesis intermediate, is often used as a synthetic raw material for dyes and fragrances, and has a good market prospect.

[0003] Currently, the publicly available synthetic routes for 1-[4-(chloromethyl)phenyl]ethanone are very limited. The traditional synthetic scheme uses p-methylacetophenone as a raw material, and chlorinates it with a chlorinating agent to obtain 1-[4-(chloromethyl)phenyl]ethanone. The raw materials and auxiliary materials are relatively expensive, the conversion efficiency is low (usually less than 20%), the selectivity is poor (isoprosthesis and multiple substitutions are prone to occur), and the separation is difficult, making it difficult to achieve large-scale industrialization. Therefore, it is of great significance to independently develop an industrial synthetic route for 4-chloromethylacetophenone. Summary of the invention

[0004] This method uses benzyl chloride as the starting material, undergoes Friedel-Crafts acylation, quenching, and distillation to obtain high-purity (purity up to 98%) 1-[4-(chloromethyl)phenyl]ethanone. The reaction equation of this method is as follows: .

[0005] The synthesis method of 1-[4-(chloromethyl)phenyl]ethanone provided by this patent includes: adding Lewis acid and acylating agent to a solvent, adding benzyl chloride dropwise at 0-40°C, quenching with water after the reaction is completed, taking the organic layer and adding alkaline solution to adjust the pH to 4-7 to ensure the stability of the product during the distillation process, taking the organic layer, concentrating to dryness under reduced pressure to remove the solvent, and distilling under reduced pressure to obtain 1-[4-(chloromethyl)phenyl]ethanone. Among them, the molar ratio of Lewis acid, acylating agent and benzyl chloride is 1-3:1.0-1.5:1. Among them, the Lewis acid is selected from aluminum trifluoromethanesulfonate or copper trifluoromethanesulfonate, and the acylating agent is selected from acetyl chloride or acetic anhydride.

[0006] Wherein, the solvent is selected from dichloromethane, chloroform, tetrahydrofuran, dichloroethane or chlorobenzene, etc. Preferably, the solvent is selected from dichloromethane or chloroform. Preferably, the acylating agent is acetyl chloride.

[0007] Preferably, the Lewis acid is aluminum triflate.

[0008] Among them, the reaction time is 4-8h.

[0009] Specifically, the reaction solution is poured into ice water for quenching, and the amount of ice water used is 7-10 times the weight of benzyl chloride.

[0010] Specifically, a saturated sodium bicarbonate solution is added to adjust the pH to 4-7.

[0011] Preferably, the temperature of the vacuum distillation is less than 120° C. to ensure the purity of the product.

[0012] Preferably, the synthesis method of 1-[4-(chloromethyl)phenyl]ethanone provided by the present invention comprises: adding aluminum trifluoromethanesulfonate to a solvent, then adding acetyl chloride, and dropping benzyl chloride at 0-40°C. After the reaction is completed, pouring the reaction solution into ice water for quenching, taking the organic layer, adding saturated sodium bicarbonate solution to adjust the pH to 4-7, taking the organic layer, concentrating to dryness under reduced pressure, and performing vacuum distillation below 120°C to obtain 1-[4-(chloromethyl)phenyl]ethanone. Wherein, the molar ratio of aluminum trifluoromethanesulfonate, acetyl chloride and benzyl chloride is 1-3:1.0-1.5:1, and the solvent is selected from dichloromethane or chloroform.

[0013] In this patent, due to the benzyl chloride and Lewis acid, the reaction degree is not high and more impurities are generated. The reaction involves the Friedel-Crafts acylation reaction between acetyl chloride and benzyl chloride and the intermolecular Friedel-Crafts alkylation reaction of benzyl chloride itself, which can reduce the Friedel-Crafts alkylation reaction under specific conditions. In addition, the positioning effect of this patent is general, and the ortho- and meta-products can be reduced under specific conditions. Under the conditions of this patent, 10-20% of ortho-products will be obtained, but meta-products will basically not be obtained; however, the boiling points of ortho-products and target products are significantly different, and they can be purified by distillation. That is, in this patent, the applicant found that more impurities would be obtained by the method of this patent; however, the applicant analyzed the product and optimized the Lewis acid, so that the impurities in the product were ortho-products and there were basically no polysubstituted products and Friedel-Crafts alkylation products, which could be separated by simple distillation. However, during distillation, it was found that both the product and the impurities were unstable. The applicant found that adjusting the pH value before distillation could improve stability, and lowering the distillation temperature could also improve stability.

[0014] This method has the following advantages: (1) The starting materials are cheap and readily available, and the reaction only requires one step, which results in low cost; (2) Purification is simple, requiring only pH adjustment and distillation, which is suitable for industrial production; (3) More than 98% of the product can be obtained through distillation (in industry, the distillation purity is usually not high, and usually multiple distillations or other subsequent treatments are required); (4) High selectivity, with a yield greater than 60% and up to 75% under optimized conditions. DETAILED DESCRIPTION

[0015] The invention is further described below through specific examples, but it should be noted that these examples are merely illustrative and do not limit the scope of the invention.

[0016] Embodiment 1: Add 1000g of dichloromethane and 711g of aluminum trifluoromethanesulfonate (1.5mol) to a 3L reaction bottle, stir evenly, add 94.2g of acetyl chloride (1.2mol), control the temperature at 0-10℃, and drop 126.6g of benzyl chloride (1.0mol) and 200g of dichloromethane into the system. After the addition is complete, gradually warm up to room temperature, and stop the reaction after 5-8h. Pour the reaction solution gradually into a 1000ml ice-water mixture, stand for separation after quenching, separate the organic layer, add saturated sodium bicarbonate solution and stir until the pH of the water layer is 5-6, separate the organic layer, and concentrate to dryness under reduced pressure to obtain an oily 1-[4-(chloromethyl)phenyl]ethanone crude product, and then distill under reduced pressure and temperature control below 120℃ to obtain 126g of light yellow oily liquid 1-[4-(chloromethyl)phenyl]ethanone, with a yield of 75% and a purity of 98.8%.

[0017] Embodiment 2: Add 1500g of chloroform and 995.4g of aluminum trifluoromethanesulfonate (2.1mol) to a 3L reaction bottle, stir evenly, add 117.8 of acetyl chloride (1.5mol), control the temperature at 0-10℃, and drop 126.6g of benzyl chloride (1.0mol) and 200g of chloroform into the system. After the addition is complete, gradually warm up to room temperature, and stop the reaction after 4-6h. Pour the reaction solution gradually into a 1500ml ice-water mixture, stand for separation after quenching, separate the organic layer, add saturated sodium bicarbonate solution and stir until the pH of the water layer is 6-7, separate the organic layer, and concentrate to dryness under reduced pressure to obtain an oily 1-[4-(chloromethyl)phenyl]ethanone crude product, and then distill under reduced pressure and temperature control below 120℃ to obtain 129.4g of light yellow oily liquid 1-[4-(chloromethyl)phenyl]ethanone, with a yield of 77% and a purity of 98.3%.

[0018] Embodiment 3: 1000g of dichloromethane and 711g of aluminum trifluoromethanesulfonate (1.5mol) were added to a 3L reaction bottle, and 214.4g of acetic anhydride (2.1mol) was added after stirring evenly. A mixed solution consisting of 126.6g of benzyl chloride (1.0mol) and 200g of dichloromethane was added dropwise to the system at a temperature of 0-10°C. After the addition was completed, the temperature was gradually raised to room temperature. The reaction was stopped after the reaction for 5-8h. The reaction solution was gradually poured into a 1000ml ice-water mixture, and after quenching, the mixture was allowed to stand for separation. After the organic layer was separated, a saturated sodium bicarbonate solution was added and stirred until the pH of the water layer was 5-6. The organic layer was separated and concentrated to dryness under reduced pressure to obtain an oily crude product of 1-[4-(chloromethyl)phenyl]ethanone, and then distilled under reduced pressure and temperature control below 120°C to obtain 107.6g of a light yellow oily liquid 1-[4-(chloromethyl)phenyl]ethanone, with a yield of 64% and a purity of 98.1%.

[0019] Embodiment 4: Add 500g of dichloromethane and 243.3g of ferric chloride (1.5mol) to a 1L reaction bottle, stir evenly, add 94.2g of acetyl chloride (1.2mol), control the temperature at 0-10℃, and drop a mixed solution consisting of 126.6g of benzyl chloride (1.0mol) and 200g of dichloromethane into the system. After the addition is complete, gradually warm up to room temperature, and stop the reaction after reacting for 5-8h. Pour the reaction solution gradually into a 1000ml ice-water mixture, stand for separation after quenching, separate the organic layer, add saturated sodium bicarbonate solution and stir until the pH of the water layer is 5-6, separate the organic layer, and concentrate to dryness under reduced pressure to obtain an oily 1-[4-(chloromethyl)phenyl]ethanone crude product, and then distill under reduced pressure and temperature control below 120℃ to obtain 72.3g of light yellow oily liquid 1-[4-(chloromethyl)phenyl]ethanone, with a yield of 43% and a purity of 96.8%.

[0020] Example 5 Add 500g of dichloromethane and 204.5g of zinc chloride (1.5mol) to a 1L reaction bottle, stir evenly, add 94.2g of acetyl chloride (1.2mol), control the temperature at 0-10℃, and drop a mixed solution consisting of 126.6g of benzyl chloride (1.0mol) and 200g of dichloromethane into the system. After the addition is complete, gradually warm up to room temperature, and stop the reaction after reacting for 5-8h. Pour the reaction solution gradually into a 1000ml ice-water mixture, stand for separation after quenching, separate the organic layer, add saturated sodium bicarbonate solution and stir until the pH of the water layer is 5-6, separate the organic layer, and concentrate to dryness under reduced pressure to obtain an oily 1-[4-(chloromethyl)phenyl]ethanone crude product, and then distill under reduced pressure and temperature control below 120℃ to obtain 58.5g of light yellow oily liquid 1-[4-(chloromethyl)phenyl]ethanone, with a yield of 35% and a purity of 95.4%.

[0021] Example 6 Add 1500g of dichloromethane and 542.3g of copper trifluoromethanesulfonate (1.5mol) to a 1L reaction bottle, stir evenly, add 94.2g of acetyl chloride (1.2mol), control the temperature at 0-10℃, and drop a mixed solution consisting of 126.6g of benzyl chloride (1.0mol) and 200g of dichloromethane into the system. After the addition is complete, gradually warm up to room temperature, and stop the reaction after reacting for 5-8h. Pour the reaction solution gradually into a 1000ml ice-water mixture, stand for separation after quenching, separate the organic layer, add saturated sodium bicarbonate solution and stir until the pH of the water layer is 5-6, separate the organic layer, and concentrate to dryness under reduced pressure to obtain an oily 1-[4-(chloromethyl)phenyl]ethanone crude product, and then distill under reduced pressure and temperature control below 120℃ to obtain 105.8g of light yellow oily liquid 1-[4-(chloromethyl)phenyl]ethanone, with a yield of 63% and a purity of 98.5%.

[0022] Example 7 Add 500g of dichloromethane and 200g of aluminum chloride (1.5mol) to a 1L reaction bottle, stir evenly, add 94.2g of acetyl chloride (1.2mol), control the temperature at 0-10℃, and drop a mixed solution of 126.6g of benzyl chloride (1.0mol) and 200g of dichloromethane into the system. After the addition is complete, gradually warm up to room temperature, and stop the reaction after 5-8h. Pour the reaction solution gradually into a 1000ml ice-water mixture, stand for separation after quenching, separate the organic layer, add saturated sodium bicarbonate solution and stir until the pH of the water layer is 5-6, separate the organic layer, and concentrate to dryness under reduced pressure to obtain an oily 1-[4-(chloromethyl)phenyl]ethanone crude product, and then distill under reduced pressure and temperature control below 120℃ to obtain 82.3g of light yellow oily liquid 1-[4-(chloromethyl)phenyl]ethanone, with a yield of 49% and a purity of 97.7%.

[0023] It can be seen from Examples 4, 5 and 7 that the selectivity of common Lewis acids such as aluminum chloride, zinc chloride and ferric chloride is not good, resulting in low product yields and low purity of some products, such as 96.8% purity of zinc chloride and 95.4% purity of zinc chloride. That is, under the conditions of this patent, a specific Lewis acid can be used to obtain a product with high yield and high purity.

[0024] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone, characterized in that the method comprises: adding a Lewis acid and an acylating agent to a solvent, dropwise adding benzyl chloride at 0-40°C, quenching with water after the reaction is completed, taking an organic layer and adding an alkaline solution to adjust the pH to 4-7, taking an organic layer, concentrating to dryness under reduced pressure, and performing vacuum distillation to obtain 1-[4-(chloromethyl)phenyl]ethanone; the molar ratio of the Lewis acid, the acylating agent and the benzyl chloride is 1-3: 1.0-1.5:1, the Lewis acid is selected from aluminum trifluoromethanesulfonate or copper trifluoromethanesulfonate, and the acylating agent is selected from acetyl chloride or acetic anhydride.

2. The method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone according to claim 1, characterized in that: The solvent is selected from dichloromethane, chloroform, tetrahydrofuran, dichloroethane or chlorobenzene.

3. The method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone according to claim 1, characterized in that: The solvent is selected from dichloromethane or chloroform.

4. The method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone according to claim 1, characterized in that: The acylating agent is acetyl chloride.

5. The method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone according to claim 1, characterized in that: The Lewis acid is aluminum trifluoromethanesulfonate.

6. The method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone according to claim 1, characterized in that: The reaction time is 4-8h.

7. The method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone according to claim 1, characterized in that: The reaction solution was poured into ice water for quenching, wherein the amount of ice water used was 7-10 times the weight of benzyl chloride.

8. The method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone according to claim 1, characterized in that: Saturated sodium bicarbonate solution was added to adjust the pH to 4-7.

9. The method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone according to claim 1, characterized in that: The temperature of the vacuum distillation is less than 120°C.

10. The method for synthesizing 1-[4-(chloromethyl)phenyl]ethanone according to claim 1, characterized in that: The method comprises: adding aluminum trifluoromethanesulfonate to a solvent, then adding acetyl chloride, and dropwise adding benzyl chloride at 0-40°C. After the reaction is completed, pouring the reaction solution into ice water for quenching, taking an organic layer, adding a saturated sodium bicarbonate solution to adjust the pH to 4-7, taking the organic layer, concentrating to dryness under reduced pressure, and performing vacuum distillation below 120°C to obtain 1-[4-(chloromethyl)phenyl]ethanone; the molar ratio of the aluminum trifluoromethanesulfonate, acetyl chloride and benzyl chloride is 1-3:1.0-1.5:1, and the solvent is selected from dichloromethane or chloroform.